Potential epigenetic mechanisms in psychotherapy: a pilot study on DNA methylation and mentalization change in borderline personality disorder

Abstract

Genetic and early environmental factors are interwoven in the etiology of Borderline Personality Disorder (BPD). Epigenetic mechanisms offer the molecular machinery to adapt to environmental conditions. There are gaps in the knowledge about how epigenetic mechanisms are involved in the effects of early affective environment, development of BPD, and psychotherapy response. We reviewed the available evidence of the effects of psychotherapy on changes in DNA methylation and conducted a pilot study in a sample of 11 female adolescents diagnosed with BPD, exploring for changes in peripheral DNA methylation of FKBP5 gene, which encodes for a stress response protein, in relation to psychotherapy, on symptomatology and underlying psychological processes. For this purpose, measures of early trauma, borderline and depressive symptoms, psychotherapy outcome, mentalization, and emotional regulation were studied. A reduction in the average FKBP5 methylation levels was observed over time. Additionally, the decrease in FKBP5 methylation observed occurred only in those individuals who had early trauma and responded to psychotherapy. The results suggest an effect of psychotherapy on epigenetic mechanisms associated with the stress response. The finding that epigenetic changes were only observed in patients with early trauma suggests a specific molecular mechanism of recovery. The results should be taken with caution given the small sample size. Also, further research is needed to adjust for confounding factors and include endocrinological markers and therapeutic process variables.

Psychobiology and Treatment of Personality Disorders and Related Prominent Traits

“…A favourable effect of psychotherapies on epigenetic mechanisms associated with the stress response has been cautiously suggested [80]. Also with reservations, results have been reported that point to possible epigenetic biomarkers predictive of the specific effect of behavioural-dialectical psychotherapy in patients with borderline or emotionally unstable personality disorder (ICD-10) [81].…”

A long but fruitful journey: From clinical psychoanalysis to public mental health in Chile

“…Second, showing the professional community and health authorities the importance of not leaving psychodynamic therapy out of Mental Health policies (de la Parra, Florenzano, & Jiménez, 2005; Jiménez, 1994). In recent years, however, we decided not to invest any more time in convincing colleagues but to build and propose empirical research models of clinical psychoanalytic hypotheses (Jiménez, Botto, Herrera et al., 2018; Jiménez & Altimir, 2019; Altimir & Jiménez, 2020, 2021; Quevedo et al., 2022) or dynamic psychotherapy models that work at the primary level of health care (de la Parra, Zúñiga, Dagnino, & Gómez‐Barris, 2021).…”

Genetic Influences on Outcomes of Psychotherapy in Borderline Personality Disorder: A Narrative Review of Implications for Personalized Treatment

“…Here, methyl group tags annex to DNA regions, governing gene activation or suppression. Research has demonstrated that epigenetic changes like DNA methylation may influence the interplay between genes and the environment and affect neurodevelopment in the context of BPD [ 18 ].…”

“…A pilot study in 2022 conducted by Quevedo in 11 females with early trauma found stress reduction seen in peripheral FKBP5 response protein methylation in response to BPD psychotherapy. The results implied that psychotherapy affects epigenetics involved in BPD's development and psychotherapeutic response [ 44 ]. A study in 2017 led by Knoblich et al, involving 88 participants (comprising 37 females and seven males diagnosed with BPD, matched with 44 healthy controls), found elevated methylation levels in APBA3 and MCF2 among those responding to a 12-week DBT program, emphasizing the predictive power of genetic indicators in BPD treatment [ 45 ].…”